DFNB66 and DFNB67 loci are non allelic and rarely contribute to autosomal recessive nonsyndromic hearing loss

We previously mapped the DFNB66 locus to an interval overlapping the DFNB67 region. Mutations in the LHFPL5 gene were identified as a cause of DFNB67 hearing loss (HL). However, screening of the coding exons of LHFPL5 did not reveal any mutation in the DFNB66 family. The objective of this study was to check whether DFNB66 and DFNB67 are distinctive loci and determining their contribution to HL. In the DFNB66 family, sequencing showed absence of mutations in the untranslated regions and the predicted promoter sequence of LHFPL5. Analysis of five microsatellites in the 6p21.31–22.3 region and screening of the LHFPL5 gene by DNA heteroduplex analysis in DHPLC revealed a novel mutation (c.89dup) in one out of 129 unrelated Tunisian families with autosomal recessive nonsyndromic (ARNS) HL. Our findings suggest that two distinct genes are responsible for DFNB66 and DFNB67 HL. These loci are likely to be a rare cause of ARNSHL.     

Re-assigning the DFNB33 locus to chromosome 10p11.23-q21.1

Homozygosity mapping is a powerful resource for mapping and identifying loci and genes responsible for autosomal recessive disorders. Nevertheless, it could result in the identification of several homozygous regions unrelated to the disease locus or non-informative regions. Previously, a genome-wide screen in a large consanguineous Jordanian family allowed us to assign the DFNB33 locus to chromosome 9q34.3. Sequencing of 23 candidate genes showed 11 SNPs in a heterozygous state in affected individuals. These results ruled out the candidate region on chromosome 9. Using additional markers, we were able to restrict the disease locus to an approximately 14 cM region at chromosome 10, located between markers D10S193 and D10S1784. A maximum LOD score of 3.99 was obtained with two markers, D10S199 and D10S220. The screening of two candidate genes, CX40.1 and FXYD4, failed to reveal any disease-causing mutations.     

Helicobacter pylori infection and risk of preeclampsia: a systematic review and meta-analysis

Objective: Helicobacter pylori is associated with many pregnancy adverse effects such as preeclampsia (PE). We performed this systematic review and meta-analysis study to assess the possible association between H. pylori infection and PE and this is the first meta-analysis to clarify this issue.

Methods: PubMed, ISI (Web of Science), SCOPUS, and Google Scholar databases were searched (up to April 2017) to identify the relevant studies. The Meta-analysis of Observational Studies in Epidemiology and Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines were used to do this study. Pooled odds ratio (OR) and 95% confidence intervals (CI) were estimated using a random-effects meta-analysis model. Heterogeneity was assessed with the χ²-based Q-test and I² statistic.

Results: A total of eight studies including 889 participants (460 preeclamptic women and 429 controls) met the eligibility criteria. A positive association was found between H. pylori infection and PE (OR: 3.35; 95% CI: 2.21–5.10). Heterogeneity was acceptable (χ²?=?13.39; I²?=?47.7, 95% CI: 0–77). In subgroup analysis, cytotoxin-associated antigen A seropositivity was a substantial risk factor for PE when immunoblotting methods (OR: 11.12; 95% CI: 5.34–23.16; χ²?=?6.42; I²?=?53.3, 95% CI: 0–85) were used, whereas it was not potential risk factor for PE when ELISA was used as a detecting method (OR: 1.11; 95% CI: 0.6–2.06; χ²?=?1.83; I²?=?0, 95% CI: 0–90).

Conclusions: This study indicated that women with H. pylori infection, especially those infected with Cag A positive strains are more likely to have PE compared with the uninfected women.     

Prediction of spontaneous preterm birth: salivary progesterone assay and transvaginal cervical length assessment after 24 weeks of gestation,another critical window of opportunity

Objectives: Measurement of salivary progesterone (SP4) levels and cervical length (CL) after 24 weeks to assess their potential predictive value among asymptomatic women at high risk of spontaneous preterm birth (PTB).

Methods: This prospective observational (noninterventional) study consecutively recruited asymptomatic women at high risk of spontaneous PTB. SP4 and CL were measured at recruitment (24–28 weeks of gestation) then repeated after 3–4 weeks. All recruited women were followed up regularly till delivery. The primary outcome measure was the occurrence of spontaneous PTB.

Results: One hundred and thirty four women completed the study, 22 (16.4%) and 32 (23.9%) women had early (<34 weeks) and late (≥34 weeks) PTB, respectively. Initially, the mean CL was 3.2?±?0.6?cm and the mean SP4 was 4062.8?±?814.6?pg/ml; with follow up, the mean CL became 3.0?±?0.6?cm and the mean SP4 became 3871.6?±?1136.9. Women with early PTB had significantly lower initial and follow up CL and SP4 measures when compared to women with late PTB and those who had birth at term. The rate of drop in SP4 and CL measurements between the two visits was also significantly higher among women with early PTB than those with late PTB and term birth. Receiver-operating characteristic (ROC) curves showed that, CL was a good predictor but SP4 was a better predictor of PTB as the area under the curve (AUC) for CL was less than that for SP4 at both visits (i.e. 0.858 and 0.868 versus 0.986 and 0.990 at the initial and follow up visits, respectively). There was a statistically significant correlation between CL and SP4 measurements. Multivariable binary logistic regression analysis revealed that follow up SP4 measurement was the only independent predictor of spontaneous PTB, and neither BMI, maternal age, SP4 nor CL were independent predictors of early spontaneous PTB.

Conclusions: After 24 gestational weeks, SP4 assessment is a simple and reliable promising tool to predict spontaneous PTB among asymptomatic high-risk women, with a little superior performance than CL measurement.     

Peripheral Blood Grafts for T Cell–Replete Haploidentical Transplantation Increase the Incidence and Severity of Cytokine Release Syndrome

T cell–replete post-transplant cyclophosphamide (PTCy)-based protocols have led to increasing use of haploidentical allogeneic hematopoietic cell transplantation (haploHCT). With this approach, bidirectional alloreactivity causing nonengraftment or severe graft-versus-host disease (GVHD) is no a longer major barrier to haploHCT. PTCy eliminates alloreactive lymphocytes but spares CD34⁺ stem cells and regulatory T lymphocytes, resulting in reliable hematopoietic recovery with relatively low incidence of GVHD. The immediate post-haploHCT course, usually before PTCy administration, is often complicated by cytokine release syndrome (CRS). The predictors of CRS and its effect on outcomes post-transplant have not been fully ascertained. We analyzed the outcomes of 66 patients who received haploHCT at our institution. Using published CRS criteria we identified 48 patients who developed CRS. In multivariate analysis peripheral blood grafts were significantly associated with grade ≥ 2 CRS, compared with bone marrow. Grade ≥ 2 CRS (compared with grade < 2) was not associated with differences in overall survival or nonrelapse mortality. Severe CRS was associated with a statistically nonsignificant trend toward higher incidences of grades III to IV acute GVHD, especially in the context of peripheral blood grafts. CRS is a common complication after T cell–replete peripheral blood haploHCT, but post-transplant survival outcomes may not be affected in those with severe CRS.     

Serologic prevalence of Ornithobacterium rhinotracheale infections in broilers and broiler breeder chickens in Kermanshah Province,west of Iran

The presence of Ornithobacterium rhinotracheale (ORT) in poultry farms in several parts of Iran has been confirmed over the last few years. The purpose of this study was to determine the presence of ORT antibodies by enzyme-linked immunosorbent assay (ELISA) in broiler and broiler breeder chickens in western parts of Iran. In a one-year period, from April 2009 to February 2010, a total of 435 blood samples were collected from 30 commercial chicken flocks (24 broiler flocks and six broiler breeder flocks) located in Kermanshah Province, west of Iran. None of the broilers and broiler breeders have been vaccinated against ORT prior to sampling. The province was divided into four geographical areas: southwest, southeast, northwest, and northeast. Flocks in each area, specifically the birds in each flock, were randomly sampled. The presence of antibodies against ORT in each serum sample was tested twice by ELISA using a commercial kit. The results revealed that 50.1 % broiler and 70.5 % broiler breeder chickens were serologically positive for ORT. Out of 347 serum samples obtained from broiler chickens, 174 (50.1 %) were positive for ORT antibodies, which represented 18 (75.0 %) of 24 examined broiler flocks. A higher rate of seropositivity (71.4 % of samples and 83.3 % of broiler flocks) was observed in the northwest. Out of 88 samples obtained from broiler breeder chickens, 62 (70.5 %) were positive for ORT antibodies, which belonged to six (100 %) of the examined broiler breeder flocks. Detection of anti-ORT antibodies among broiler breeders was significantly higher than that of broilers.     

'Pressure-flow'-triggered intracellular Ca2+ transients in rat cardiac myocytes: possible mechanisms and role of mitochondria

Cardiac myocytes, in the intact heart, are exposed to shear/fluid forces during each cardiac cycle. Here we describe a novel Ca(2+) signalling pathway, generated by 'pressurized flows' (PFs) of solutions, resulting in the activation of slowly developing ( approximately 300 ms) Ca(2+) transients lasting approximately 1700 ms at room temperature. Though subsequent PFs (applied some 10-30 s later) produced much smaller or undetectable responses, such transients could be reactivated following caffeine- or KCl-induced Ca(2+) releases, suggesting that a small, but replenishable, Ca(2+) pool serves as the source for their activation. PF-triggered Ca(2+) transients could be activated in Ca(2+)-free solutions or in solutions that block voltage-gated Ca(2+) channels, stretch-activated channels (SACs), or the Na(+)-Ca(2+) exchanger (NCX), using Cd(2+), Gd(3+), or Ni(2+), respectively. PF-triggered Ca(2+) transients were significantly smaller in quiescent than in electrically paced myocytes. Paced Ca(2+) transients activated at the peak of PF-triggered Ca(2+) transients were not significantly smaller than those produced normally, suggesting functionally separate Ca(2+) pools for paced and PF-triggered transients. Suppression of nitric oxide (NO) or IP(3) signalling pathways did not alter the PF-triggered Ca(2+) transients. On the other hand, mitochondrial metabolic uncoupler FCCP, in the presence of oligomycin (to prevent ATP depletion), reversibly suppressed PF-triggered Ca(2+) transients, as did the mitochondrial Ca(2+) uniporter (mCU) blocker, Ru360. Reducing agent DTT and reactive oxygen species (ROS) scavenger tempol, as well as mitochondrial NCX (mNCX) blocker CGP-37157, inhibited PF-triggered Ca(2+) transients. In rhod-2 AM-loaded and permeabilized cells, confocal imaging of mitochondrial Ca(2+) showed a transient increase in Ca(2+) on caffeine exposure and a decrease in mitochondrial Ca(2+) on application of PF pulses of solution. These signals were strongly suppressed by either Na(+)-free or CGP-37157-containing solutions, implicating mNCX in mediating the Ca(2+) release process. We conclude that subjecting rat cardiac myocytes to pressurized flow pulses of solutions triggers the release of Ca(2+) from a store that appears to access mitochondrial Ca(2+).     

Fetal mid-thigh soft-tissue thickness: a novel method for fetal weight estimation

Purpose

To derive a novel formula for fetal weight estimation utilizing the linear measurement of mid-thigh soft-tissue thickness (STT).

Methods

300 women, with singleton uncomplicated pregnancy, were included in a prospective cross-sectional study. The study included four consecutive phases: phase (1) validated the original Scioscia’s formula, phase (2) derived a novel modified formula for fetal weight estimation, phase (3) validated the novel modified formula, and phase (4) evaluated the agreement between the modified and original formulae.

Results

A statistically significant correlation was found between actual fetal weight (AFW) and various sonographic biometric measurements including mid-thigh STT (r ² = 0.656, p < 0.001), femur length (FL) (r ² = 0.573, p < 0.001), bi-parietal diameter (BPD) (r ² = 0.250, p < 0.001), abdominal circumference (AC) (r ² = 0.310, p < 0.001), and estimated fetal weight (EFW) using the original Scioscia’s formula (r ² = 0.644, p < 0.001). The modified formula showed a better signed % difference (median = ?0.41 %, IQR ?1.88 to 2.03) than the original formula (median = ?0.51 %, IQR ?2.33 to 2.00). It was noted that, using the original formula, 88.7 % of the sample had absolute error below 5 and 98.3 % of the sample had absolute error below 10 %. On the other hand, using the modified formula, 87.3 % of the sample had absolute error below 5 %, while 97.3 % had absolute error below 10 %. The agreement between the two formulae was moderate as 134 patients out of 150 had similar ranking (κ = 0.57).

Conclusion

Fetal mid-thigh SST is a simple, useful, and easily applicable parameter for fetal weight estimation.     

The influence of accommodative insufficiency on reading

Background: It is not known how accommodative insufficiency influences reading performance. Methods: Reading eye movements were recorded before and after treatment for accommodative insufficiency in 12 school children (eight to 16 years). During the eight‐week treatment period all subjects wore a +1.00 D addition when reading. Results: Large variations in reading patterns were found. Despite successful accommodative treatment (p < 0.001), no correlation was found to suggest improved reading velocity. Discussion: Three case reports will be presented and the implications discussed.